Landa Iñigo
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Curr Opin Endocr Metab Res. 2023 Jun;30. doi: 10.1016/j.coemr.2023.100460. Epub 2023 May 26.
Thyroid cancers are often initiated by the acquisition of a BRAF mutation. BRAF-driven thyroid tumors display a wide range of behaviors, from the slow-growing papillary carcinomas to the highly aggressive anaplastic. Mutations in the promoter of (telomerase reverse transcriptase) gene were discovered a decade ago and identified as prevalent events in thyroid cancers. Multiple studies showed that promoter mutations, particularly when co-occurring with BRAF, are markers of poor prognosis across thyroid cancer subtypes, and can be implemented for routine clinical stratification. Mechanistically, promoter mutations reactivate telomerase expression via the differential recruitment of transcriptional complexes. Re-expression of TERT impacts tumor biology, plausibly via both the well-known function of telomerase maintaining telomeres and by affecting other cancer-relevant processes.
甲状腺癌通常由获得BRAF突变引发。BRAF驱动的甲状腺肿瘤表现出广泛的行为，从生长缓慢的乳头状癌到高度侵袭性的间变性癌。（端粒酶逆转录酶）基因启动子的突变在十年前被发现，并被确定为甲状腺癌中的常见事件。多项研究表明，启动子突变，特别是与BRAF同时出现时，是甲状腺癌各亚型预后不良的标志物，可用于常规临床分层。从机制上讲，启动子突变通过转录复合物的差异募集重新激活端粒酶表达。TERT的重新表达影响肿瘤生物学，可能是通过端粒酶维持端粒的众所周知的功能以及影响其他与癌症相关的过程。
